title: Prognostic factors of 'high-grade' Ta bladder cancers according to the WHO 2004 classification: are these equivalent to 'high-risk' non-muscle-invasive bladder cancer?
abstract: OBJECTIVE
  To determine the impact of prognostic factors of a series of high-grade Ta non-muscle-invasive bladder cancers (NMIBCs) according to the new International Society of Urological Pathology (ISUP) 1998/WHO 2004 grading system (previously classified as either TaG2 or TaG3).
  
  
  METHODS
  One hundred and thirty-one high-grade Ta (105 G2 and 26 G3) cases were identified after independent review by two pathologists. Univariable and multivariable Cox regression models addressed recurrence and progression-free survival. Progression was defined as appearance of any T ≥1 recurrence after complete TUR (type 1) or occurrence of T ≥2 (type 2).
  
  
  RESULTS
  Ten-year recurrence, type-1 and type-2 progression-free survival were 60, 75 and 95%, respectively. The previous grading system (G3 vs. G2) significantly predicted type 1 progression in the univariate model only. In the multivariate model, Ki67 was the only independent predictor of progression according to both definitions (HR = 5.25, p = 0.002 and HR = 6.16, p = 0.03, respectively).
  
  
  CONCLUSIONS
  High-grade Ta NMIBC as defined by the WHO 2004 grading system cannot be equated with high-risk NMIBC. The risk of progression to muscle-invasive disease (type 2) is low, more in keeping with an intermediate-risk category of NMIBC. The previous WHO 1973 subcategorization into G2 and G3 is of little help in the prediction of outcome. Ki67 is a strong independent predictor of progression worthy of consideration for a clinical setting.
authors.affiliation: Department of Urology 1, A.O.U. San Giovanni Battista, Turin, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Gontero
authors.forename: Arianna
authors.initials: A
authors.lastname: Gillo
authors.forename: Chiara
authors.initials: C
authors.lastname: Fiorito
authors.forename: Marco
authors.initials: M
authors.lastname: Oderda
authors.forename: Donatella
authors.initials: D
authors.lastname: Pacchioni
authors.forename: Giovanni
authors.initials: G
authors.lastname: Casetta
authors.forename: Francesca
authors.initials: F
authors.lastname: Peraldo
authors.forename: Andrea
authors.initials: A
authors.lastname: Zitella
authors.forename: Alessandro
authors.initials: A
authors.lastname: Tizzani
authors.forename: Fulvio
authors.initials: F
authors.lastname: Ricceri
mesh_terms: D000368:Aged; D015331:Cohort Studies; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D016016:Proportional Hazards Models; D012306:Risk; D012720:Severity of Illness Index; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000145:classification / Q000175:diagnosis* / Q000473:pathology; D014944:World Health Organization